PCIF1

protein-coding

phosphorylated CTD interacting factor 1, the group of Protein phosphatase 1 regulatory subunits|7BS N6-adenosine DNA/RNA methyltransferases

Gene summary

Enables RNA polymerase II C-terminal domain phosphoserine binding activity; S-adenosyl-L-methionine binding activity; and mRNA (2'-O-methyladenosine-N6-)-methyltransferase activity. Involved in mRNA processing; negative regulation of translation; and positive regulation of translation. Located in intercellular bridge; microtubule cytoskeleton; and nucleoplasm. [provided by Alliance of Genome Resources, Jul 2025]

Previous symbols:

C20orf67

MANE transcript

NM_022104.4

Inheritance

ClinVar variants

U:85B:10

Top phenotype

Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalities

gnomAD constraint

pLI —, LoF o/e 0.05

Max pathogenic AF

—

Genomic locus

chr20:45,934,683-45,948,023

External References & Databases

Ensembl (ENSG00000100982)

Transcript & Mutation Effects

hg38 • Region Span ~13.3 kb

Loading mutation effect viewer...

GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

No GenCC data available for this gene.

Clinical Genomic Database (CGD)

Neurodevelopmental disorder with hypotonia, facial dysmorphism, and brain abnormalitiesAR

Manifestation: Cardiovascular; Craniofacial; Musculoskeletal; Neurologic; Ophthalmologic

Intervention: Cardiovascular

Rationale: Among other features, the condition can include cardiomyopathy, and awareness may allow early diagnosis and management

Refs: 28940097; 29808498; 30520571; 32985083

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PCIF1 variants in ClinVar

1 Conditions Cataloged

not specifiedTotal: 92

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_022104.4. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			1 clinvar	8 clinvar		9
missense			81 clinvar	2 clinvar		83
nonsense						0
start loss						0
frameshift						0
splice donor/acceptor (+/-2bp)			3 clinvar			3
Total	0	0	85	10	0	95

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 66 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_022104.4	RefSeq	NP_071387.1	15	MANE Select
ENST00000372409.8	Ensembl	ENSP00000361486.3	15	MANE Select
ENST00000479348.2	Ensembl	ENSP00000480607.1	6	Standard
ENST00000904032.1	Ensembl	ENSP00000574091.1	15	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

negative regulation of phosphatase activity

Cellular Component

nucleus
nucleoplasm
microtubule cytoskeleton
intercellular bridge

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000372409
Coding exons: 15
Length: 13396
Individuals with no LoFs: 125733
Homozygous LoFs: 0
Heterozygous LoFs: 5
Defined: 125738
p: 0.0000199

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	2.41	315	461	0.684	0.0000308	4570
Missense (PolyPhen)		65	165.22	0.39341		1584
Synonymous	-0.316	188	183	1.03	0.0000120	1400
Loss of Function	5.61	2	40.6	0.0493	0.00000235	420

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.000059	0.000058	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.000054	0.000054	rare
Finnish	0.000046	0.000046	rare
European (Non-Finnish)	0.0000088	0.0000088	rare
South Asian	0	0.0	absent
Other	0	0.0	absent

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: May play a role in transcription elongation or in coupling transcription to pre-mRNA processing through its association with the phosphorylated C-terminal domain (CTD) of RNAPII largest subunit.;

Recessive Scores

pRec: 0.100

Intolerance Scores

LoFtool: 0.00592
RVIS EVS: -0.84
RVIS percentile EVS: 11.28

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: E
Indispensability score: 0.969

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium